Recent estimates suggest that the number of U.S. men with erectile dysfunction may be near 10 to 20 million, and inclusion of individuals with partial erectile dysfunction increases the estimate to about 30 million. The male erectile response is initiated by the action of neurons, or nerve cells (i.e., neuronal action), and maintained by a complex interplay between events involving blood vessels (i.e., vascular events) and events involving the nervous system (i.e., neurological events).
It is parasympathetic neuronal action that initiates the male erectile response. The cavernous nerves (designated greater and lesser) supply parasympathetic fibers to the corpora cavernosum and corpus spongiosum, the erectile tissue in the penis containing large interspaces capable of being distended with blood. The cavernous nerves arise from the spinal cord, and researchers have elucidated the location of the spinal cord neurons that ultimately give rise to the cavernous nerves.
In 1985, Lue labeled the cavernous nerves of dogs with horseradish peroxidase, which was transported in a retrograde fashion to the spinal cord nuclei cell bodies. The neurons thus labeled were mediolateral autonomic neurons at T12-L3 and S1-S3.
In a 1992 study of three male patients with complete spinal cord lesions (in the thoracic region), Stief found that spinal cord stimulation of the anterior (i.e., ventral) roots of S2 to 55 produced erection in all 3 patients. [Stief, et al., “The influence of anterior root stimulation (S2) in deafferented spinal cord injury men on cavernous electrical activity.” Journal of Urology, 1992 July; 148(1):107-110.] Stief further indicated that, using a pulse amplitude of 30 volts and a pulse width of 400 μsec, stimulation frequencies of 12-30 Hz produced full erection, while 7-8 Hz and 45 Hz produced only partial erection. However, all three patients of this study received treatment for bladder spasticity, which included deafferentation (i.e., dorsal rhizotomy, or lesioning) of the dorsal (sensory) roots from S2 to 35, and implantation of U-shaped electrodes around the anterior roots of S2 to S5. These electrodes were implanted intradurally. In addition, the stimulator used (the Brindley stimulator) is strictly radio-frequency controlled.
An article by Creasey in 1993 entitled “Electrical stimulation of sacral roots for micturition after spinal cord injury” [Urol Clin North America, 1993 August; 20(3):505-515] focused on restoration of bladder function. Two stimulator systems were used: the Finetech implant (also known as the Brindley stimulator, as used in the Stief study) and the Medtronic implant. The article says “Erectile function is reported to be unaffected by the Medtronic implant.” The Finetech implant did affect erectile function. However, as mentioned earlier, the Finetech system is strictly radio-frequency controlled, and is implanted “using an intradural approach to facilitate the separation of anterior from posterior roots.” While the article mentions that “electrodes suitable for extradural implantation adjacent to the mixed sacral nerves” have been developed, the article does not appear to report on any use of such electrodes. With the Finetech implant, the “electrodes are placed around these [sacral anterior] roots . . . [and c]ables from the electrodes are brought out through a grommet in the dura, which is then closed.” In addition, “[t]he procedure is usually combined with intradural division of the posterior roots of S2-S5.” In other words, as with the Stief study, methods used in this study also included rhizotomy of afferents, e.g., posterior roots (a.k.a., dorsal roots), or rhizotomy of dorsal root ganglion or ganglia.
In a 1998 study of the sacral neural pathways mediating penile erection in the cat, Tai found that the greatest change in cavernous sinus pressure (CSP) was elicited by stimulation of the S1 ventral roots rather than the S2 or S3 spinal roots. [Tai, et al. “Penile erection produced by microstimulation of the sacral spinal cord of the cat.” IEEE Trans Rehabil Eng, 1998 December; 6(4):374-381.] Tai further reported that, “Maximal CSP responses were evoked by microstimulation in the middle of the S1 ventral horn, 1.6-2.8 mm below the cord surface and midway between the midline and the lateral edge of the gray matter.” The best responses were achieved with stimulus intensities of 50-150 μA, at a pulse width of 200 psec, and at frequencies of 30-40 Hz, and occurred after a delay of 8-40 seconds. However, as common defined by those of skill in the art, “microstimulation,” as used by Tal, is provided by a fine-tipped “microelectrode” (Tai's had a surface area of 200-400 μm2) producing very low amplitude currents, generally less than 200 μA (Tai used 50-150 μA). The other stimulation used by Tai was provided by a “hook electrode.” No chronic, implantable stimulator was used. Tai used both the microelectrode and hook electrode to acutely stimulate the ventral roots intradurally.
Parasympathetic activity allows erection by relaxation of smooth muscle (i.e., muscle found in the walls of internal organs, blood vessels, hair follicles, etc. that contracts without voluntary control) and dilation of the helicine arteries, which are coiled arteries found in the erectile tissue of the penis. The dilation of the arteries causes greatly increased blood flow through the erectile tissue, which leads to expansion of the three cylinders of erectile tissue in the penis (i.e., the corpora cavernosum and the corpus spongiosum). As the corpora cavernosum and the corpus spongiosum expand, the venous structures draining the penis are compressed against the fascia surrounding each of the erectile tissues (i.e., the tunica albuginea of the corpora cavernosum and the tunica albuginea of the corpus spongiosum). Thus, the outflow of blood is restricted, and the internal pressure increases. This vein-obstruction process is referred to as the corporal veno-occlusive mechanism.
Conversely, constriction of the smooth muscle and helicine arteries induced by sympathetic innervation (i.e., stimulation by nerves) from the hypogastric nerves, for example, from certain nerves of the inferior hypogastric plexus, may make the penis flaccid.
Erectile dysfunction has a number of causes, both physiological and psychological, and in many patients the disorder may be multifactorial. The causes include several that are essentially neurologic in origin. Damage to the pathways used by the autonomic nervous system to innervate the penis may interrupt “psychogenic” erection initiated by the central nervous system. Psychogenic erection has a mental or emotional origin, rather than a physical basis. Lesions (e.g., injury, infection, or disease) of the somatic nervous pathways (i.e., any of the nerves associated with sensation or motion) may impair reflexogenic erections (i.e., involuntary, instinctive physiological response to a stimulus) and may interrupt tactile sensation needed to maintain psychogenic erections. Spinal cord lesions may produce varying degrees of erectile failure depending on the location and severity of the lesions.
Not only lesions affect erectile ability; disorders leading to peripheral neuropathy may also impair neuronal innervation of the penis. Peripheral neuropathy is a disorder or abnormality of the part of the nervous system constituting the nerves outside the central nervous system and including the cranial nerves, the spinal nerves, and the sympathetic and parasympathetic nervous systems. Peripheral neuropathy may also impair neuronal innervation of the sensory afferents—the nerves that conduct impulses from the periphery of the body to the brain or spinal cord, transmitting impulses from sense organs to nerve centers. Peripheral neuropathy is a potential sequela of a number of diseases, e.g., diabetes mellitus.
The endocrine system (glands such as the thyroid, adrenal, or pituitary, having hormonal secretions that pass directly into the bloodstream), particularly the production of androgens (steroid hormones, such as testosterone or androsterone, that control the development and maintenance of masculine characteristics), appears to play a role in regulating sexual interest, and may also play a role in erectile function.
In men of all ages, erectile failure may diminish willingness to initiate sexual relationships because of fear of inadequate sexual performance or rejection. Because males, especially older males, are particularly sensitive to the social support of intimate relationships, withdrawal from these relationships because of such fears may have a negative effect on their overall health.
Some forms of erectile dysfunction are treated with medication, with varying degrees of success. For instance, the well-publicized oral medication VIAGRA® (active ingredient sildenafil citrate) requires an hour to exert its full effects, and it may have significant side effects such as abnormal vision, flushing, headache, and diarrhea.
Intracavernosal injection therapy, in which a patient injects vasodilator substances (e.g., papaverine) into the corpora of the penis, suffers a high rate of patient dropout, as does the therapeutic application of vacuum constriction devices. Several forms of penile prostheses are available, including semirigid, malleable, and inflatable, but these have significant problems with mechanical failure, infection, and device erosion.
Various stimulation devices have been proposed for treating sexual dysfunction. Some devices stimulate through the skin, such as intrarectal stimulation devices. Other devices require significant surgical procedures for placement of electrodes, leads, and processing units. For instance, as discussed earlier, studies have used intradural implantation of electrodes, which can lead to complications such as cerebral spinal fluid leakage, increased risk of infection, among other things. As another example also discussed earlier, studies have included rhizotomy (i.e., lesioning) of Adorsal roots or other structures. Known devices may also require an external apparatus that needs to be strapped or otherwise affixed to the skin. While several patents exist regarding stimulators for treatment of erectile dysfunction, the inventors know of no chronic, fully implantable neurostimulator device that is commercially available.